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Biochemical and functional characterization of 1-benzyl substituted trimetoquinol affinity analogs on rat and human beta-adrenoceptors.

The site of interaction for the 1-(3',4',5'-trimethoxybenzyl) group of trimetoquinol (TMQ) with beta-adrenoceptors (beta-ARs) is important for the rational design of highly potent and beta3-AR-selective analogs. 1-Benzyl ring-substituted TMQ analogs were evaluated for binding affinities and biochemical activities (cyclic AMP accumulations) in Chinese hamster ovary (CHO) cells expressing the rat and human beta3-AR, and for functional activities on isolated rat tissues. Binding affinities (K1 approximately 0.055 to 1.5 microM) for the rat beta3-AR and potencies for adenylyl cyclase activation (K(act) approximately 0.43 to 2;5 nM) of the 3'-monoiodo or 3',5'-diiodo derivatives with 4'-isothiocyanato-, 4'-amino, 4'-acetamido, or 4'-alpha-haloacetamido substitutions were higher than those of (-)-isoproterenol, and comparable to those of BRL 37344 [(+/-)-(R*,R*-[4-[2-[[2-(3-chlorophenyl)-2-hydroxy-ethyl]amino]propyl]ph enoxy]-acetic acid sodium]. A similar rank order of binding affinities (K(i) approximately 0.11 to 2.5 microM) and potencies (K(act) approximately 0.45 to 9.5 nM) was obtained for TMQ analogs on the human beta3-AR. The 4'-acetamido and 4'-alpha-chloroacetamido analogs of 3',5'-diiodoTMQ were more potent than (-)-isoproterenol in rat atria (beta1-AR) and rat trachea (beta2-AR) and exhibited partial agonist activities, whereas full agonist activities were observed in rat esophageal smooth muscle (EC50 approximately 2-8 nM, beta3-AR). 4'-alpha-Chloroacetamido-3',5'-diiodoTMQ-mediated chronotropic responses in atria were sustained and resistant to washout. Further, the 4'-alpha-chloroacetamido and 4'-alpha-bromoacetamido analogs of 3',5'-diiodoTMQ demonstrated significant concentration-dependent irreversible binding to the rat beta3-AR. Reversible beta-AR agonists such as (-)-isoproterenol, BRL 37344, and 4'-acetamido-3',5'-diiodoTMQ or nucleophilic 1-amino acids (lysine, glutathione, cysteine) did not protect against this irreversible binding. Thus, the lipophilic 1-benzyl ring of TMQ analogs interacts with a hydrophobic region of the beta-AR that may represent an exo-site or an allosteric binding site.

Adrenergic beta-Agonists↗

Acute hemodynamic effects of pulsed delivery of low flow nasal nitric oxide in children with pulmonary hypertension.

We studied 8 children, ages 8 months to 14 years, during cardiac catheterization in order to determine the acute hemodynamic effects of pulsed nasal cannula delivery of nitric oxide (NO) in children with pulmonary hypertension. NO was administered by continuous mask or pulsed nasal cannula in random order. All patients effectively triggered the NO pulsing device. Pulsed delivery of inhaled NO lowered mean pulmonary artery pressure and pulmonary vascular resistance as effectively as mask delivery of NO. Pulsed inhaled NO delivery may potentially be useful for the long-term domiciliary treatment of pulmonary hypertension in children.

Administration, Inhalation↗

Adenosine triphosphate-dependent potassium channel modulation and cardioplegia-induced protection of human atrial muscle in an in vitro model of myocardial stunning.

OBJECTIVES: Although adenosine triphosphate-dependent potassium channel openers have been shown to enhance cardioplegic protection in animal myocardium, there is a lack of data on human cardiac tissues. We aimed at determining, on human atrial muscle, whether adenosine triphosphate- dependent potassium channels are involved in protection caused by high-potassium cardioplegia and whether adenosine triphosphate-dependent potassium channel activation might improve cardioplegic protection in an in vitro model of myocardial stunning. METHODS: Human atrial trabeculae were obtained from adult patients undergoing cardiac operations. In an organ bath at 37 degrees C, the preparations were subjected to 60 minutes of hypoxia at a high stimulation rate either in Tyrode solution (control, n = 17) or in St Thomas' Hospital solution without additives (n = 6) or associated with 100 nmol/L bimakalim (n = 7) or 1 micromol/L glibenclamide (n = 7), followed by 60 minutes of reoxygenation and 15 minutes of positive inotropic stimulation with 1 micromol/L dobutamine. RESULTS: Atrial developed tension was reduced by hypoxia to 27% +/- 5% of baseline and incompletely recovered after reoxygenation to 38% +/- 7%, whereas dobutamine restored contractility to 74% +/- 7% of basal values. St Thomas' Hospital solution with or without bimakalim improved developed tension after reoxygenation and dobutamine (P <.0001 vs control), whereas glibenclamide inhibited these protective effects of cardioplegic arrest (P =.001 vs St Thomas' Hospital solution). After reoxygenation, the protective effect of bimakalim disappeared at a high pacing rate (400- and 300-ms cycle length) but recovered during dobutamine superfusion. CONCLUSIONS: Adenosine triphosphate-dependent potassium channels are likely involved in the cardioprotective effects of cardioplegia in human atrial trabeculae and adenosine triphosphate-dependent potassium channel activation with bimakalim used as an additive to cardioplegia enhanced protection.

Adenosine Triphosphate↗

Evaluation of diastolic dysfunction and repolarization dispersion in Behcet's disease.

Behcet's disease is a generalized chronic inflammatory disease characterized by genital, ocular, and cardiovascular involvement. Recently, left ventricular diastolic dysfunction, ventricular arrhythmia and sudden cardiac death have been documented in Behcet's disease. From January 1996 to May 1998, we investigated left ventricular systolic and diastolic function, valvular heart disease, ischemic heart disease and repolarization dispersion in 71 cases, 40 men and 31 women (mean age, 36.8+/-10.3 years) with Behcet's disease. All of the results were compared with the control group of 33 men and 22 women (mean age, 37.9+/-9.6 years). Exercise stress test or myocardial perfusion scintigraphy was performed for the documentation of ischemia. All the patients and the controls were recorded by M-mode, 2-D and Doppler echocardiography. Ventricular wall thickness, valvular apparatus, left ventricular systolic and diastolic parameters were evaluated. Repolarization dispersion parameters were calculated as the difference between maximal and minimal values of QT from 12-lead electrocardiogram recording at baseline, immediate and end of recovery from the exercise stress tests. The measured parameters were compared with the control group by using statistical methods. In the Behcet's group of 22 patients (31%) E/A ratio was <1. In the control group of five cases (10%) E/A ratio was <1 (P=0.003). In the Behcet's group isovolumic relaxation time (IRT) and mitral deceleration time (MDT) were longer than the control group (P=0.002, P=0.041, respectively). A mean QT of 368+/-30 ms and mean QT dispersion of 73+/-14 ms in the patient group compared with a mean QT of 395+/-39 ms and mean QT dispersion of 38+/-12 ms in the controls. There was no statistical difference between the mean QT values of the patient and control groups however, ventricular dispersion parameters in the Behcet's patients were longer than in the controls (P<0.001). There was also statistical significance for the QT dispersion between the Behcet's patients with and without diastolic dysfunction (P<0.01). In conclusion, the study reveals that the patients with Behcet's disease have a high incidence of increased diastolic dysfunction and repolarization dispersion. A positive correlation may exist between diastolic dysfunction and QT dispersion.

Adult↗

Left ventricular pressure-volume relationship in a murine model of congestive heart failure due to acute viral myocarditis.

OBJECTIVES: This study, performed in a murine model of encephalomyocarditis virus myocarditis, used a new Millar 1.4F conductance-micromanometer system for the in vivo determination of the left ventricular (LV) pressure-volume relationship (PVR). BACKGROUND: Viral myocarditis is an important cause of congestive heart failure and may lead to dilated cardiomyopathy. However, the hemodynamic changes associated with its acute phase have not been analyzed in detail. METHODS: Four-week-old DBA/2 mice were inoculated with EMCV (day 0). Serial hemodynamic measurements, compared with uninfected control mice were made on days 0, 1, 3, 4, 5, 7, 9, 12, and 14. RESULTS: On day 1, the hearts of infected mice manifested enhanced contractile function, decreased LV compliance, and abnormal diastolic function with increased LV end-diastolic pressure (EDP). Mean stroke index, ejection fraction (EF), and cardiac index (CI) were significantly higher than in uninfected control mice (p < 0.05). Contractile function decreased from days 4 to 14. On day 7, when hemodynamic abnormalities consistent with heart failure culminated, end-diastolic volume (EDV), EDP, and EDPVR were significantly higher, and CI, EF, end-systolic pressure (ESP), and ESPVR significantly lower in the infected than in control mice. Heart rate remained comparable in both groups. Although heart failure receded between day 9 and day 14, ESPVR, ESP, and EF remained significantly depressed up to day 14, and EDV and EDP remained significantly higher. CONCLUSIONS: These hemodynamic data provide new insights into the pathophysiology of acute viral myocarditis and may be useful in the development of therapeutic interventions.

Animals↗

Perioperative cardiac pacing using an atrioventricular pacing pulmonary artery catheter.

An atrioventricular pacing thermodilution pulmonary artery catheter was evaluated in 40 patients undergoing cardiac surgery. The catheter was inserted in all study patients in a timely fashion without difficulty and functioned well during the perioperative period. Before the start of cardiopulmonary bypass, atrial capture was achieved in 98% of the patients (threshold mean 4.9 mA), ventricular capture in 100% (threshold mean 3.0 mA) and atrioventricular sequential (AVS) pacing in 98%. After cardiopulmonary bypass, atrial capture was achieved in 95% of the patients (threshold mean 5.2 mA), ventricular pacing in 100% (threshold mean 3.1 mA), and sequential pacing in 95%. In 27 patients in whom cardiac outputs were recorded, cardiac index increased an average of 45% (range 8% to 95%) with atrial or AVS pacing over ventricular pacing alone. In 11 patients, extended atrial pacing was used postoperatively, the longest for 93 hours. No major complications could be attributed to the study catheter. Minor complications included diaphragmatic stimulation in one patient and supraventricular tachycardia, possibly related to atrial pacing postoperatively, in one patient. These data suggest that this catheter/pacing system is effective and reliable for hemodynamic monitoring and temporary atrial or AVS pacing. In addition, the atrial pacing probe can be used perioperatively to record atrial electrograms to facilitate the diagnosis of supraventricular tachyarrhythmias.

Aged↗

The effects of intravenous nitroglycerin and isosorbide dinitrate on hemodynamics and myocardial metabolism.

Myocardial ischemia before and during coronary artery surgery is significant, because patients who develop perioperative myocardial ischemia have an increased incidence of postoperative myocardial infarctions. Thus, the prevention of ischemic episodes is of great importance. This study was undertaken to (1) compare the effects of intravenous nitroglycerin (NTG) with isosorbide dinitrate (ISDN); (2) investigate if the continuous infusion of nitrates had beneficial effects on cardiac performance and metabolism; and (3) compare the control of blood pressure with the nitrates versus halothane during a standardized anesthetic. Twenty-one patients participated in the study, and all had the following: a radial arterial catheter, peripheral venous catheter, 7F pulmonary artery catheter, and Baim coronary sinus flow catheter. The study was carried out in the prebypass period beginning with awake measurements of baseline parameters, and ending after median sternotomy. The patients were divided into three groups: group 1 received an infusion of NTG; group 2 received an infusion of ISDN; and group 3, the control, received neither nitrate, but halothane was added to control hemodynamics. Measurements were made at the following time intervals: (1) baseline; (2) after 5 minutes of the nitrate infusions while awake (groups 1 and 2); (3) after induction of anesthesia, laryngoscopy, and intubation; and (4) after median sternotomy. In groups 1 and 2, the nitrates were infused at 0.1 mg/kg/h for 5 minutes. Thereafter, blood pressure control and treatment of episodic hypertension were achieved by alteration of the rate of nitrate infusions, or, in group 3, by 0.5% to 2% of inspired halothane.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Experimental and numerically modeled effects of altered loading conditions on pulmonary venous flow and left atrial pressure in patients with mitral regurgitation.

Pulmonary venous flow measured by pulsed-wave Doppler transesophageal echocardiography reflects the effects of mitral regurgitation on left atrial pressure contour. To assess the relationship between pulmonary venous flow and left atrial pressure in patients with mitral regurgitation under altered loading conditions, we studied 25 patients with 3+ or 4+ mitral regurgitation and a control group by measuring pulmonary venous flow with transesophageal echocardiography and left atrial pressures after administering saline solution (n = 6), nitroglycerin (n = 6), phenylephrine (n = 6), or nitroprusside (n = 7). After administration, the left atrial pressure v wave increased in the group given phenylephrine, concomitant with an increased diastolic flow. In contrast, the left atrial pressure v wave decreased in the group given nitroglycerin, concomitant with a decreased diastolic flow. Changes in diastolic flow were closely related to changes in the left atrial pressure v wave under all loading conditions (r = 0.91; p < 0.0001). Numeric modeling of left atrial pressure and pulmonary venous diastolic flow corroborated the experimental findings. We conclude that changes in pulmonary venous diastolic flow are closely related to changes in the left atrial pressure v wave in mitral regurgitation, under altered loading conditions.

Adult↗

Importance of Doppler analysis of transmitted atrial waveforms prior to placement of central venous access catheters.

PURPOSE: To assess the sensitivity of Doppler flow analysis of the axillary and internal jugular veins to screen for clinically occult thoracic central veno-occlusive disease and predict successful placement of central access catheters. MATERIALS AND METHODS: Sixty-seven patients underwent both duplex sonographic evaluation of the axillary and internal jugular veins and contrast venography prior to placement of a central venous catheter. Duplex evaluation included visual evidence of veno-occlusive disease as well as the presence or absence of normal transmitted polyphasic atrial waves and respiratory variation of flow. Diagnostically adequate venograms were available for comparison with the duplex sonograms in 168 access routes (access site plus downstream conduit veins). The contrast venograms and sonograms were compared by using retrospective blinded interpretation. Outcome of attempted catheter placement was tabulated. RESULTS: Directed sonographic imaging of the axillary and internal jugular vein allowed detection of access route veno-occlusive disease with a sensitivity of only 33.3%. Alternatively, when Doppler flow analysis found atrial waveforms that were not polyphasic, central conduit occlusive disease was detected with a sensitivity of 79.6%. Monophasic atrial waveforms were associated with a 25% failure rate of catheterization due to central vein occlusive disease, whereas polyphasic atrial waveforms were correlated with a 100% success rate for catheter placement. CONCLUSION: In asymptomatic patients, sonographic imaging alone misses most instances of central veno-occlusive disease. However, Doppler flow analysis of transmitted atrial waveforms substantially improved the sensitivity. A normal polyphasic atrial waveform virtually excludes the possibility of a more central venous occlusion or stenosis greater than 80% and ensures an adequate route for central venous catheterization.

Adult↗

The hemodynamic effects of isotonic exercise using hand-held weights in patients with heart failure.

BACKGROUND: Controversy surrounds the use of resistance exercise in patients with heart failure because of concerns that increases in rate-pressure product and systemic vascular resistance might lead to increased afterload and decreased cardiac output. METHODS: Following pharmacologic left ventricular unloading therapy using a pulmonary artery catheter, 34 patients with advanced heart failure performed isotonic weightlifting exercise at 50%, 65%, and 80% of the calculated one repetition maximum. Measurements were made of hemodynamics, ST segment, rate-pressure product, serum norepinephrine, rating of perceived exertion, and dysrhythmias following each exercise set. RESULTS: Repeated analysis of variance showed significant increases in systolic blood pressure (p = 0.0005), diastolic blood pressure (p = 0.01), rate-pressure product (p = 0.005); serum norepinephrine (p = 0.004), and rating of perceived exertion (p = 0.0005). However, systemic vascular resistance and cardiac output did not change significantly (p>0.05). Pulmonary capillary wedge pressures, the incidence of dysrhythmias, and ST segments did not significantly differ from baseline. No patients experienced angina or dyspnea during the study. CONCLUSIONS: Isotonic exercise using hand-held weights was well tolerated hemodynamically and clinically, and no patients experienced adverse outcomes during exercise.

Adrenergic alpha-Agonists↗

Conduction velocity around the tricuspid valve annulus during type 1 atrial flutter: defining the location of areas of slow conduction by three-dimensional electroanatomical mapping.

BACKGROUND: Conduction velocity (CV) around the tricuspid valve annulus (TVA) during type 1 atrial flutter (AFL) has been shown to be slowest in the tricuspid valve-inferior vena cava (TV-IVC) isthmus, compared to the septal or free wall segments of the TVA. However, fiber orientation in the triangle-of-Koch suggests that the inferior septum and medial TV-IVC isthmus should be the most slowly conducting segments around the TVA. METHODS: To test this hypothesis we evaluated CV around the TVA during type 1 atrial flutter in 11 patients, using an electro-anatomical mapping system (Carto). CV was first calculated in 4 segments around the TVA including the TV-IVC isthmus, lateral free wall, superior free wall and septum, and then calculated in 8 segments around the TVA including medial (MI) and lateral isthmus (LI), inferior (IL) and superior lateral (SL) free wall, lateral (LS) and medial superior (MS) free wall, and superior (SS) and inferior septum (IS). Statistical comparison of CV from these multiple segments was made by one-way analysis of variance. RESULTS: Measured in 4 segments around the TVA, mean CV (m/sec) in the TV-IVC isthmus (0.81 +/- 0.23) and the septum (0.93 +/- 0.18) was significantly slower than CV in the lateral free wall (1.16 +/- 0.23) and superior free wall (1.10 +/- 0.20), and CV in the TV-IVC isthmus was significantly slower than in the septum (p < 0.05). However, when analyzed in 8 segments, mean CV in the MI (0.56 +/- 0.16) and IS (0.59 +/- 0.24) was significantly (p < 0.05) slower than in all other segments including the LI (1.06 +/- 0.46), IL (1.17 +/- 0.40), SL (1.15 +/- 0.40), LS (1.04 +/- 0.25), MS (1.15 +/- 0.28), and SS (1.26 +/- 0.36) segments. CONCLUSIONS: Consistent with previous reports, CV around the TVA during type 1 AFL was slowest in the TV-IVC isthmus, compared to the septum, superior and lateral free wall regions. However, when the TVA was further subdivided into 8 segments, CV in the MI and IS segments was significantly slower than in all other segments around the TVA. These observations more precisely define the regions of slow conduction in human type 1 AFL, and are consistent with the known anisotropy and slow conduction in the Triangle of Koch.

Anisotropy↗

Endogenous muscarinic activity attenuates adrenergic inotropic effects in field stimulated atrial myocardium from children with congenital heart defects.

To analyse the possible influence of endogenous muscarinic activity on the inotropic effects of endogenously released noradrenaline in field stimulated myocardial preparations from atria of children with congenital heart defects, we studied the maximal effect of the muscarinic antagonist atropine (1.5 micromol L(-1)). Maximal force of contraction increased by 12.8 +/- 2.0% (SEM), while the maximal rate of development of the force increased by 16.7 +/- 2.7% (SEM). Time to half maximal developed force was 57 +/- 5 s (SEM). Time to peak force, time to relax to the 20% level and relaxation time all decreased significantly after atropine. Compared with endogenous adrenoceptor stimulation alone, the combined effects of partial muscarinic and adrenergic receptor stimulation thus were moderate reductions of the maximal force of contraction and maximal rate of development of the force and increased time to peak force, time to relax to the 20% level and relaxation time. The main effect of the endogenous muscarinic activity probably was to attenuate the effect of the beta-adrenoceptor stimulation. The endogenous muscarinic activity in field stimulated atrial preparations from children is significant, and has to be taken into account in experimental set-ups.

Acetylcholine↗

Supranormal natriuretic response to volume expansion in vagotomized and renal-denervated rats.

1. To investigate the participation of both vagal cardiopulmonary baroreceptor activity and efferent renal sympathetic nerve activity (ERSNA) in the natriuretic response to saline volume expansion (SVE), three series of experiments were undertaken in anaesthetized rats. 2. In the first two series of experiments, the natriuretic (series A) and ERSNA (series B) responses to SVE were evaluated in both sham operated and cervical bilateral vagotomized rats. The acute experiment consisted of two baseline (BL) periods, treatment (sham control (CTR) or real cervical bilateral vagotomy), a volume expansion phase (Ringer's solution, 10% bodyweight) and a postexpansion phase. The results of these two series indicate that vagotomy significantly enhances basal ERSNA (37 +/- 8%; P < 0.05 vs BL) and significantly attenuates the renal sympathoinhibitory response (by approximately 50%; P < 0.05 vs CTR) but not the natriuretic response to SVE, suggesting the potential expression of a vagotomy induced compensatory natriuretic mechanism. 3. To assess this, the natriuretic response to SVE was evaluated in chronic sham operated or renal denervated groups of rats in which vagotomy was or was not performed (series C). There were no differences among groups in either systemic haemodynamics or plasma protein concentration. Vagotomy plus chronic renal denervation induced a supranormal natriuretic and diuretic response (approximately 30%; P < 0.01) to SVE when compared with similar natriuretic and diuretic responses of the remaining groups. 4. These data support the idea that, in intact rats on a normal sodium diet, neither cardiopulmonary baroreceptors nor renal nerves are necessary for the elimination of an acute intravenous isotonic sodium load and indicate that during SVE the activation of vagal cardiopulmonary baroreceptors exerts an inhibitory effect on both ERSNA and the expression of a natriuretic mechanism. Such a natriuretic mechanism is expressed only when SVE is induced in vagotomized rats (compensating for the vagotomy mediated antinatriuretic effects of an enhanced ERSNA), but is unmasked only when, in addition, renal nerves are chronically transected. All of this offers an efficient element of safety in eliminating an acute isotonic sodium load when cardiopulmonary baroreceptors are severed.

Animals↗

Single lead DDD pacing using electrodes with longitudinal and diagonal atrial floating dipoles.

In this study, an assessment was made of the possibilities of single lead DDD pacing in two groups: a group of 15 patients in whom a lead with a longitudinal atrial "floating" dipole was implanted, and another group of 10 patients with a lead with a diagonal atrial "floating" dipole. In both groups, the electrodes were connected to a SLD generator. At discharge, atrial capture was achieved with the unipolar mode in 17 of 25 patients, whereas in the group carrying the longitudinal atrial dipole, atrial capture was achieved with the overlapping biphasic impulses (OLBI) system in 12 of 15 patients and in all 10 patients in the group with the diagonal atrial dipole. At 3 months, atrial capture was achieved with the unipolar mode in 13 of 22 patients (5.75 +/- 1.77 V/0.5 ms), whereas with the OLBI system atrial capture was achieved in 8 of 13 patients carrying the longitudinal atrial dipole (3.11 +/- 1.13 V/0.5 ms), and in 8 of the 9 patients carrying the diagonal atrial dipole (2.80 +/- 0.69 V/0.5 ms). In this study, the use of the OLBI system led to a significant reduction of atrial threshold (P < 0.0001). Phrenic stimulation is the main untoward effect reported during single lead DDD pacing, a lower incidence being detected in the group carrying the diagonal atrial dipole (10 vs 35.7%, P = NS). Other limitations of this form of pacing could result from a crossed stimulation phenomenon detected in a patient during single lead DDD pacing.

Aged↗

Implantation of the undulation pump total artificial heart in the goat.

The undulation pump total artificial heart (UPTAH) was developed by using small-size continuous-flow displacement-type blood pumps (undulation pump). To clarify and improve the problems accompanied by the implantation in the chest, 14 animal experiments were performed on goats weighing 41.3-79.2 kg. The UPTAH could be implanted in the chest of all goats and was driven with a modulation pulsatile mode. The first problem was the atrial suction effect. This problem could be prevented to some extent by developing the soft disk and by improving atrial cuffs. An automatic detection and releasing of the atrial suction effect was also tried. The next problem was acute lung edema accompanied by the postural change of the animal. Development of the automatic control of left atrial pressure could prevent this problem. Small blood leakage from a pinpoint hole in the seal membrane was the next problem. Improvement of the manufacturing procedure of the membrane prevented this. With these improvements, a 10 day survival could be obtained with this unique implantable total artificial heart.

Acute Disease↗

Vagal nerve activity recording in the awake condition for the control of an artificial heart system.

To detect useful information for an artificial heart control system, we paid attention to the autonomic nervous system. For stable recording, we used vagal nerve activity in chronic animal experiments using healthy adult goats in an awake condition because this nerve was sufficiently bold and large enough. Vagal nerve discharges were successfully recorded from awake goats. They were synchronized with respiration and responded to the hemodynamic changes induced by drug administration, suggesting that they may provide useful information for an artificial heart control algorithm. For automatic control, some time delay plays a vitally important role. Thus, predictive control for an artificial heart system may be desirable. It may be embodied by the use of autonomic nerve information.

Action Potentials↗